Understanding the impact of airway inflammation on vagal afferents is of particular interest because these neurons play an important role in the life-threatening reflex bronchoconstriction that occurs during anaphylactic reactions. During these reactions, airway vagal afferents are excited and modified by unidentified products released from, or generated by, mast cell activation. Two functionally distinct populations of vagal afferents innervating the airway, nodose and jugular ganglion neurons (NGNs and JGNs) will be identified with retrograde fluorescence tracers and their electrophysiological and pharmacological properties studied before and following chronic allergic airway inflammation. We will also determine whether chemical communication between nodose somata is somatotopically organized and influenced by inflammation in vitro and in vivo. Airway projecting NGNs and JGNs will be studied in vitro using voltage clamp recording in conjunction with microfluorimetry to measure intracellular calcium. Calcium and second messengers will be analyzed and manipulated in order to clarify the signal pathway of NK-2 tachykinin receptor (NK2R)-mediated currents (Icat) unmasked by mast cell activation, or by serotonin. Icat channels will be characterized by their cation selectivity and single channel properties and compared to transient receptor potential channels (TRPC). NK2Rs signaling cascade to activate TRPC in HEK293 cells will be compared with NK2R pathway activating Icat in NGNs. These studies will add to our understanding of allergic inflammation-induced neuroplastic changes in vagal afferents. This study of the signal molecules and mechanisms underlying the neuroplasticity in vagal afferents will also shed new light on the pathobiology of myriad hypersensitivity and inflammatory diseases.